Featured Publications
Molecular topography of an entire nervous system
Taylor SR, Santpere G, Weinreb A, Barrett A, Reilly MB, Xu C, Varol E, Oikonomou P, Glenwinkel L, McWhirter R, Poff A, Basavaraju M, Rafi I, Yemini E, Cook SJ, Abrams A, Vidal B, Cros C, Tavazoie S, Sestan N, Hammarlund M, Hobert O, Miller DM. Molecular topography of an entire nervous system. Cell 2021, 184: 4329-4347.e23. PMID: 34237253, PMCID: PMC8710130, DOI: 10.1016/j.cell.2021.06.023.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCaenorhabditis elegansCaenorhabditis elegans ProteinsFluorescent DyesGene Expression Regulation, DevelopmentalGenes, ReporterLarvaNervous SystemNeuronsNeuropeptidesNucleotide MotifsRegulatory Sequences, Nucleic AcidRNA-SeqSignal TransductionTranscription FactorsTranscription, GeneticConceptsGene expressionSpecific gene familiesCis-regulatory elementsNeuron-specific gene expressionIndividual neuron classesSingle-cell resolutionGene expression profilesNeuron classesGene familyAdhesion proteinsNeuropeptide genesExpression profilesExpression dataEntire nervous systemCombinatorial expressionMolecular topographyNervous systemSynaptic specificityNeuropeptide receptorsExpressionPotential roleWiring diagramComputational approachGenesProteinActivation of the CaMKII-Sarm1-ASK1-p38 MAP kinase pathway protects against axon degeneration caused by loss of mitochondria
Ding C, Wu Y, Dabas H, Hammarlund M. Activation of the CaMKII-Sarm1-ASK1-p38 MAP kinase pathway protects against axon degeneration caused by loss of mitochondria. ELife 2022, 11: e73557. PMID: 35285800, PMCID: PMC8920508, DOI: 10.7554/elife.73557.Peer-Reviewed Original ResearchConceptsMAPK pathwayLoss of mitochondriaMitochondrial defectsUnbiased genetic screenMAP kinase pathwayCell-specific activationTrafficking complexGenetic screenCEBP-1Kinase pathwayUnderlying cellular mechanismsCellular mechanismsL-type voltage-gated calcium channelsMitochondriaVoltage-gated calcium channelsPathwayUNCAxon degenerationCaenorhabditisActivationCalcium channelsFurther analysisTraffickingSuppressesCaMKIIA Functional Non-coding RNA Is Produced from xbp-1 mRNA
Liu X, Beaudoin JD, Davison CA, Kosmaczewski SG, Meyer BI, Giraldez AJ, Hammarlund M. A Functional Non-coding RNA Is Produced from xbp-1 mRNA. Neuron 2020, 107: 854-863.e6. PMID: 32640191, PMCID: PMC7486263, DOI: 10.1016/j.neuron.2020.06.015.Peer-Reviewed Original Research
2024
Organization of a functional glycolytic metabolon on mitochondria for metabolic efficiency
Wang H, Vant J, Zhang A, Sanchez R, Wu Y, Micou M, Luczak V, Whiddon Z, Carlson N, Yu S, Jabbo M, Yoon S, Abushawish A, Ghassemian M, Masubuchi T, Gan Q, Watanabe S, Griffis E, Hammarlund M, Singharoy A, Pekkurnaz G. Organization of a functional glycolytic metabolon on mitochondria for metabolic efficiency. Nature Metabolism 2024, 6: 1712-1735. PMID: 39261628, DOI: 10.1038/s42255-024-01121-9.Peer-Reviewed Original ResearchConceptsO-GlcNAc transferaseO-GlcNAcylation sitesGlycolytic metabolonO-GlcNAcylationEnzyme O-GlcNAc transferaseOuter mitochondrial membraneDynamic O-GlcNAcylationPost-translational modificationsReduced ATP generationMitochondrial ATP productionMetabolic efficiencyEnergy-demanding tissuesCellular energy sourceOGT activityMitochondrial associationRegulatory domainMitochondrial membraneMultiple cell typesATP generationATP productionMitochondrial functionMitochondrial couplingMetabolonCell typesGlucose fluxPolarized localization of kinesin-1 and RIC-7 drives axonal mitochondria anterograde transport
Wu Y, Ding C, Sharif B, Weinreb A, Swaim G, Hao H, Yogev S, Watanabe S, Hammarlund M. Polarized localization of kinesin-1 and RIC-7 drives axonal mitochondria anterograde transport. Journal Of Cell Biology 2024, 223: e202305105. PMID: 38470363, PMCID: PMC10932739, DOI: 10.1083/jcb.202305105.Peer-Reviewed Original ResearchConceptsKinesin-1C. elegansN-terminal domainRetrograde trafficAnterograde trafficTransport mitochondriaMitochondria transportPolar localizationMiro-1CRISPR engineeringMitochondria localizationDisordered regionsMitochondriaTransport complexMitochondria distributionAxonal transportAnterograde transportAnterograde axonal transportMotor complexMiroAdaptorCRISPRGenesLocal and dynamic regulation of neuronal glycolysis in vivo
Wolfe A, Koberstein J, Smith C, Stewart M, Gonzalez I, Hammarlund M, Hyman A, Stork P, Goodman R, Colón-Ramos D. Local and dynamic regulation of neuronal glycolysis in vivo. Proceedings Of The National Academy Of Sciences Of The United States Of America 2024, 121: e2314699121. PMID: 38198527, PMCID: PMC10801914, DOI: 10.1073/pnas.2314699121.Peer-Reviewed Original ResearchConceptsGlycolytic stateEnergy stressEnergy metabolismConditions of energy stressDynamic regulationNeuronal functionIndividual cell typesMitochondrial localizationGenetic analysisSubcellular regionsRegulatory enzymeCell-autonomousNeuronal identityGlycolysisCell typesMetabolic stateImaging dynamic changesMetabolismLiving organismsIn vivoCellsEnergy landscapeIndividual neuronsEnzymeDynamic changes
2023
The neuropeptidergic connectome of C. elegans
Ripoll-Sánchez L, Watteyne J, Sun H, Fernandez R, Taylor S, Weinreb A, Bentley B, Hammarlund M, Miller D, Hobert O, Beets I, Vértes P, Schafer W. The neuropeptidergic connectome of C. elegans. Neuron 2023, 111: 3570-3589.e5. PMID: 37935195, PMCID: PMC7615469, DOI: 10.1016/j.neuron.2023.09.043.Peer-Reviewed Original ResearchConceptsNervous systemSynaptic wiring diagramGene expression datasetsReceptor-ligand interactionsStudied neuronsKey network hubNeuronal connectionsSignaling cascadesBrain functionInput connectivityNeuromodulatory signalingChemical synapsesPeptidergic neuromodulationBiochemical analysisEssential roleNeural basisNeuropeptidesConnectomeNetwork hubsWiring diagramSimilar patternA kinesin-1 adaptor complex controls bimodal slow axonal transport of spectrin in Caenorhabditis elegans
Glomb O, Swaim G, Munoz LLancao P, Lovejoy C, Sutradhar S, Park J, Wu Y, Cason S, Holzbaur E, Hammarlund M, Howard J, Ferguson S, Gramlich M, Yogev S. A kinesin-1 adaptor complex controls bimodal slow axonal transport of spectrin in Caenorhabditis elegans. Developmental Cell 2023, 58: 1847-1863.e12. PMID: 37751746, PMCID: PMC10574138, DOI: 10.1016/j.devcel.2023.08.031.Peer-Reviewed Original ResearchStructure-function analysis of ceTIR-1/hSARM1 explains the lack of Wallerian axonal degeneration in C. elegans
Khazma T, Grossman A, Guez-Haddad J, Feng C, Dabas H, Sain R, Weitman M, Zalk R, Isupov M, Hammarlund M, Hons M, Opatowsky Y. Structure-function analysis of ceTIR-1/hSARM1 explains the lack of Wallerian axonal degeneration in C. elegans. Cell Reports 2023, 42: 113026. PMID: 37635352, PMCID: PMC10675840, DOI: 10.1016/j.celrep.2023.113026.Peer-Reviewed Original ResearchConceptsC. elegansCryoelectron microscopy structureNematode C. elegansC. elegans neuronsStructure-function analysisMicroscopy structureNADase activityMolecular mechanismsElegansCellular NADModel animalsSpeciesAxon degenerationWallerian axonal degenerationOrthologsOctamerProteinSARM1DivergenceNADSARMExpressionActivityAxonal degeneration
2018
Functional Genome-wide Screen Identifies Pathways Restricting Central Nervous System Axonal Regeneration
Sekine Y, Lin-Moore A, Chenette DM, Wang X, Jiang Z, Cafferty WB, Hammarlund M, Strittmatter SM. Functional Genome-wide Screen Identifies Pathways Restricting Central Nervous System Axonal Regeneration. Cell Reports 2018, 24: 269. PMID: 29972787, DOI: 10.1016/j.celrep.2018.06.079.Peer-Reviewed Original Research
2016
Inhibiting poly(ADP-ribosylation) improves axon regeneration
Byrne AB, McWhirter RD, Sekine Y, Strittmatter SM, Miller DM, Hammarlund M. Inhibiting poly(ADP-ribosylation) improves axon regeneration. ELife 2016, 5: e12734. PMID: 27697151, PMCID: PMC5050021, DOI: 10.7554/elife.12734.Peer-Reviewed Original ResearchConceptsNovel intrinsic regulatorAxon regenerationDLK functionChemical inhibitionIntrinsic regulatorRegeneration pathwayPARG expressionIntrinsic regenerative potentialDLK signalingCritical functionsPARGRegenerative potentialPARP inhibitorsProteinPARPMammalian cortical neuronsRegenerationMotor neuronsGABA neuronsPolymeraseCortical neuronsSignalingRegulatorSpeciesNeuronsAxon regeneration in C. elegans: Worming our way to mechanisms of axon regeneration
Byrne AB, Hammarlund M. Axon regeneration in C. elegans: Worming our way to mechanisms of axon regeneration. Experimental Neurology 2016, 287: 300-309. PMID: 27569538, PMCID: PMC5136328, DOI: 10.1016/j.expneurol.2016.08.015.Peer-Reviewed Original ResearchConceptsC. elegansC. elegans researchC. elegans modelSimple nervous systemMammalian nervous systemConserved genomeElegansElegans modelRegeneration responseAxon regenerationCellular mechanismsRegeneration researchTransparent bodyNervous systemRegenerationGenomeFundamental questionsSpeciesMechanismTechnical advancesRegeneration studiesPotential future directions
2015
RNA ligation in neurons by RtcB inhibits axon regeneration
Kosmaczewski SG, Han SM, Han B, Meyer B, Baig HS, Athar W, Lin-Moore AT, Koelle MR, Hammarlund M. RNA ligation in neurons by RtcB inhibits axon regeneration. Proceedings Of The National Academy Of Sciences Of The United States Of America 2015, 112: 8451-8456. PMID: 26100902, PMCID: PMC4500288, DOI: 10.1073/pnas.1502948112.Peer-Reviewed Original Research
2014
A multi-channel device for high-density target-selective stimulation and long-term monitoring of cells and subcellular features in C. elegans
Lee H, Kim SA, Coakley S, Mugno P, Hammarlund M, Hilliard MA, Lu H. A multi-channel device for high-density target-selective stimulation and long-term monitoring of cells and subcellular features in C. elegans. Lab On A Chip 2014, 14: 4513-4522. PMID: 25257026, PMCID: PMC4213302, DOI: 10.1039/c4lc00789a.Peer-Reviewed Original ResearchThe RtcB RNA ligase is an essential component of the metazoan unfolded protein response
Kosmaczewski SG, Edwards TJ, Han SM, Eckwahl MJ, Meyer BI, Peach S, Hesselberth JR, Wolin SL, Hammarlund M. The RtcB RNA ligase is an essential component of the metazoan unfolded protein response. EMBO Reports 2014, 15: 1278-1285. PMID: 25366321, PMCID: PMC4264930, DOI: 10.15252/embr.201439531.Peer-Reviewed Original ResearchConceptsUnfolded protein responseProtein responseRNA ligationIRE-1 branchesMultiple essential processesRNA ligase RtcBXBP-1 mRNACaenorhabditis elegansRNA functionRtcBMRNA fragmentsTarget RNARNA sequencesXBP-1RNA ligaseTRNAEssential processEssential componentMaturationElegansLifespanMutantsLigaseVivo modelXBP1Syndecan Promotes Axon Regeneration by Stabilizing Growth Cone Migration
Edwards TJ, Hammarlund M. Syndecan Promotes Axon Regeneration by Stabilizing Growth Cone Migration. Cell Reports 2014, 8: 272-283. PMID: 25001284, PMCID: PMC4127196, DOI: 10.1016/j.celrep.2014.06.008.Peer-Reviewed Original ResearchAxon regeneration in C. elegans
Hammarlund M, Jin Y. Axon regeneration in C. elegans. Current Opinion In Neurobiology 2014, 27: 199-207. PMID: 24794753, PMCID: PMC4122601, DOI: 10.1016/j.conb.2014.04.001.Peer-Reviewed Original ResearchBidirectional thermotaxis in Caenorhabditis elegans is mediated by distinct sensorimotor strategies driven by the AFD thermosensory neurons
Luo L, Cook N, Venkatachalam V, Martinez-Velazquez LA, Zhang X, Calvo AC, Hawk J, MacInnis BL, Frank M, Ng JH, Klein M, Gershow M, Hammarlund M, Goodman MB, Colón-Ramos DA, Zhang Y, Samuel AD. Bidirectional thermotaxis in Caenorhabditis elegans is mediated by distinct sensorimotor strategies driven by the AFD thermosensory neurons. Proceedings Of The National Academy Of Sciences Of The United States Of America 2014, 111: 2776-2781. PMID: 24550307, PMCID: PMC3932917, DOI: 10.1073/pnas.1315205111.Peer-Reviewed Original ResearchInsulin/IGF1 Signaling Inhibits Age-Dependent Axon Regeneration
Byrne AB, Walradt T, Gardner KE, Hubbert A, Reinke V, Hammarlund M. Insulin/IGF1 Signaling Inhibits Age-Dependent Axon Regeneration. Neuron 2014, 81: 561-573. PMID: 24440228, PMCID: PMC3924874, DOI: 10.1016/j.neuron.2013.11.019.Peer-Reviewed Original ResearchMeSH KeywordsAgingAnimalsAnimals, Genetically ModifiedCaenorhabditis elegansCaenorhabditis elegans ProteinsDisease Models, AnimalForkhead Transcription FactorsGene Expression RegulationGreen Fluorescent ProteinsHumansImmunosuppressive AgentsInsulinInsulin-Like Growth Factor INerve DegenerationNerve RegenerationPhosphotransferases (Alcohol Group Acceptor)PTEN PhosphohydrolaseSignal TransductionSirolimusTime FactorsTranscription FactorsAxon Regeneration Genes Identified by RNAi Screening in C. elegans
Nix P, Hammarlund M, Hauth L, Lachnit M, Jorgensen EM, Bastiani M. Axon Regeneration Genes Identified by RNAi Screening in C. elegans. Journal Of Neuroscience 2014, 34: 629-645. PMID: 24403161, PMCID: PMC3870940, DOI: 10.1523/jneurosci.3859-13.2014.Peer-Reviewed Original ResearchConceptsRNAi-based screenCandidate gene screenAnalysis of mutantsGrowth-inhibiting functionComplex molecular eventsCell-intrinsic factorsCaenorhabditis elegansC. elegansAxon regenerationGene candidatesRNAi screeningMembrane dynamicsMAP kinaseΒ-spectrinRegeneration genesGene screenMolecular eventsGenesElegansRobust regenerationMature neuronsMutantsMammalian CNSAntagonistic activityPathway